P17 CLONAL PLASMA-CELLS IN STEM CELL APHERESIS AS A PREDICTOR OF PROGRESSION IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS ELEGIBLE FOR AUTOLOGOUS STEM CELL TRANSPLANTATION
Authors: S. Pilerci, I. Attucci, L. Pengue, B. Peruzzi, R. Caporale, S. Bencini, M. Messeri, A. Buzzichelli, R. Boncompagni, C. Nozzoli, A.M. Vannucchi, E. Antonioli
Journal: HemaSphere (2023)

Background: Flow-cytometry is considered crucial for monitoring multiple myeloma (MM) patients, in particularly for evaluation of minimal residual disease (MRD) [1]. Routinely MRD on bone marrow aspirate is the optimal method for assessing depth of response and identifying higher risk of relapse [2]. There are also emerging data about the prognostic role of peripheral plasmacell count on flow-cytometry at diagnosis of MM and after treatment [3]. However, so far limited information is available on the use of flow cytometric MRD for the research of clonal plasma cells on stem cell apheresis as well as its clinical significance. Aim: Our purpose is to determine whether the contamination of apheresis product with clonal plasma cells predicts the risk of MM disease progression or impacts on patients’ overall survival (OS). Methods: We retrospectively analysed 75 newly MM patients diagnosed at our Center between July 2017 and November 2021. The multiparameter flow cytometry, with a sensitivity of 10(-5), was applied after induction therapy on both bone marrow samples and on apheresis product in order to evaluate the MRD status. Results: The median age was 60 years and all the patients were treated with triplet induction regimens (89% VTD, 5% VRD, 4% KRD, 2% PAD), followed by autologous stem cell transplantation (ASCT). Stem cell harvest was performed following cyclophosphamide and G-CSF mobilization. Sixty-two patients (91%) received maintenance therapy with lenalidomide and 6 (8%) with daratumumab. Among 75 patients included in the study, 64% and 36% of them achieved MRD positivity and negativity on bone marrow (mMRD), respectively. MRD status on apheresis (aMRD) was negative in 61 patients (81%) and positive in 14 (19%). All patients with positive aMRD had a concomitant mMRD positivity. The median follow-up was 28 months (range, 7 to 58) and progression free survival (PFS) at 24 months was 90% (95% confidence interval [CI], 86 to 94) versus 50% (95% CI, 35 to 65) for the patients aMRD-negative versus those aMRD-positive, respectively (p < 0.001). The OS at 24 months was 98% (95% CI, 96 to 100) in the aMRD negative cases and 74% (95% CI, 61 to 87) in the aMRD-positive (p=0.007). According to mMRD status, PFS at 24 months was 94% (95% CI, 88 to 100) and 75% (95% CI, 68 to 82) in the mMRD negative and positive, respectively (p=0.16). There was no statistically significant difference between the two groups according to other prognostic factors (ISS disease stage and cytogenetic profile) and maintenance therapy. Univariate analysis identified only the aMRD positivity as risk factor for reduced PFS. Conclusion: PFS data showed that the rate of progression was higher in the group of aMRD- positive patients, suggesting a potential deleterious role for graft contamination. Instead, mMRD status had not a significant impact on PFS. These results need to be confirmed in a larger prospective study with quadruplet induction regimen daratumumab-based, in order to provide a larger applicability of aMRD monitoring.[1] Moor I. et al. Peripheral flow-MRD status at the time of autologous stem cell collection predicts outcome in multiple myeloma. Bone Marrow Transplant. 2018 Dec;53(12):1599-1602. [2] Turner R. et al. The Utility of Euroflow MRD Assessment in Real-World Multiple Myeloma Practice. Front Oncol. 2022 May 18;12:820605. [3] Li J. et al. Prognostic value of circulating plasma cells in patients with multiple myeloma: a meta-analysis. PLoS ONE. 2017;12:e0181447.